Exam 2 11/2 Antimicrobial Therapy Flashcards

1
Q

Previous Exam question

What part of the bacteria is most important to maintain osmotic pressure?

A

Cell wall

Wrong answer is cell membrane

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2
Q

Previous exam question

Which cells recognize virally infected cells?

A

CD8/CTL

Recognize MHC I (endogenous antigens, check inside cell)

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3
Q

Previous exam question

Which immune cell does both phagocytosis and antigen presentation?

A

Macrophages

Neutrophils do phagocytosis but do not do APC!

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4
Q

Narrow Spectrum

A

Limited activity; works against small subset of bacteria

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5
Q

Broad spectrum

A

Work against greater variety of bacteria

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6
Q

________ agents inhibit bacterial replication

A

Bacteriostatic

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7
Q

________ agents kill bacteria

A

Bactericidal

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8
Q

Why is it important to consider minimum bactericidal concentration (MBC)?

A

Too many bacteria would be killed, including commensal bacteria (which are good for us and also help to prevent infections)

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9
Q

Minimum bactericidal concentration

A

lowest concentration of an antibacterial agent required to kill a particular bacterium

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10
Q

What is the goal of antimicrobial chemotherapy?

A

Selective toxicity - can be given to humans with reasonable safety while having toxic effects on specific microorganisms

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11
Q

Antibacterial is a broad class of:

A

Antimicrobials

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12
Q

Penicillin binding proteins

A

membrane-associated proteins involved in the biosynthesis of peptidoglycan

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13
Q

Different bacteria have different _____, which makes them have different susceptibility to beta lactams

A

PBPs

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14
Q

Beta lactam antibiotics block active site of ____ in order to prevent ____

A

PBPs, transpeptidase, etc.; cell wall synthesis

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15
Q

List the 5 beta-lactam antibiotics

A
  • penicillins
  • cephalosporins
  • cephamycins
  • carbapenems
  • monobactams
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16
Q

Penicillins consist of a beta lactam ring (___-membered ring) bound directly to thiazolidine, a ___ -membered ring

A

4; 5

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17
Q

What differentiates various penicillins?

A

Different R groups
(Ex. Penicillin, amoxycillin, etc)

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18
Q

True or false: Beta lactam antibiotics are all cell wall inhibitors, but not all cell wall inhibitors are beta lactams

A

True - for example, vancomycin works against cell wall but is not a beta lactam

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19
Q

True or false: cephalosporins contain a beta lactam ring

A

True

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20
Q

_____ are composed of a beta lactam ring (4M) fused with dihydrothiazine ring (6M)

A

Cephalosporins

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21
Q

Which antibiotic is similar to cephalosporins?

A

Cephamycins

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22
Q

Cephalosporins and cephamycins are both resistant to:

A

Many beta lactamases

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23
Q

Many gram-negatives are now developing resistance via _______________ which is conferred by ___________________

A
  • beta-lactamase (bacterial enzymes)
  • R (resistance)-plasmid
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24
Q

Carbapenems are a broad/narrow spectrum β-lactam antibiotic

A

Broad

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25
Q

TEST QUESTION: Monobactams are a broad/narrow spectrum β-lactam antibiotic

A

Narrow

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26
Q

Monobactams are active against ______. ______ and ______ are resistant

A

Aerobic gram negatives; anaerobes and gram positives

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27
Q

What antibiotic is widely used in dentistry?

A

Penicillins

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28
Q

All penicillins share problem of _________

A

Allergy

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29
Q

1 most reported drug allergy

A

Penicillin

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30
Q

Minor reaction to penicillin that is most common _____; second most common ____

A

GI upset; rashes

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31
Q

True or false: with a penicillin allergy, severe reactions are common such as anaphylaxis and seizure

A

False - severe reactions are rare

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32
Q

_____ of patients are sensitive to penicillin - why?

A

10%; cross reactivity to cephalosporins and other beta lactam antibiotics

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33
Q

What are the ways that bacteria show resistance to beta lactams - which method is most common/easiest?

A
  • block interaction of PBP and antibiotic
  • modification of binding
  • hydrolysis by beta lactamase (Most common)
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34
Q

How many beta lactamases or penicillinases exist that confer resistance to beta lactams?

A

About 200

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35
Q

There are 4 main classes of β-lactamases/penicillinase.
1. What is the most common?
2. Which class is the most resistant?

A
  1. Class A
  2. Class C (extended spectrum Beta lactamases)
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36
Q

Penicillinases have minimal activity against _______

A

Cephalosporins

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37
Q

What organisms produce Class A beta lactamases?

A

Gram-negative rods, Escherichia, Klebsiella

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38
Q

B-lactamase inhibitors

A
  • clavulanic acid
  • sulbactam
  • tazobactam
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39
Q

Augmentin

A

Clavulanic acid + amoxicillin
(blocks penicillinase and transpeptidase)

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40
Q

Pharmacokinetics - what is bioavailability

A

A measure of the extent of drug absorption for a given drug and route (from 0% to 100%)

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41
Q

Penicillins and cephalosporins: excretion

A

Renal (mostly unchanged > 80%)
Half life 30-90 min

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42
Q

Vancomycin works against what bacteria

A

Streptomyces orientalis

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43
Q

Vancomycin has a different mechanism way of inhibiting cell wall formation, instead of disrupting the β-lactam ring it binds:

A

Terminal D-ala-D-ala residues on gram-positive organisms

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44
Q

Some bacteria (Lactobacillus, Enterococcus faecalis) have Intrinsic resistance to Vancomycin: instead of D-ala-D-ala residues at the terminus they have

A

D-alanine-D-serine

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45
Q

True or false: MRSA have acquired resistance to vancomycin and are now VRSA

A

True - plasmid genes confer VanA and VanB

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46
Q

Bacitracin is a _____ inhibitor and is effective against

A

polypeptide cell wall inhibitor; gram-positive - blocks bactoprenol

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47
Q

Vancomycin is a _____ inhibitor

A

Glycopeptide cell wall inhibitor

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48
Q

Bacitracin should be applied as ____ only

A

Topical
Should not be ingested because it blocks enolase

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49
Q

Polymixin is a _____ inhibitor

A

Polypeptide cell wall inhibitor

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50
Q

Polymixin disrupts ____ so it is effective against gram-negative bacteria

A

LPS

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51
Q

Polymyxin is _____________ so it is mainly for topical use

Excretion is _____________

A

nephrotoxic; renal

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52
Q

Isoniazid is a ______ inhibitor

A

Mycobacteria cell wall inhibitor

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53
Q

Ethionamide is a derivative of

A

Isoniazid

54
Q

Isoniazid blocks synthesis of:

A

Mycolic acid
(works against Mycobacteria tuberculosis)

55
Q

Ethambutol is a _____ inhibitor

A

Mycobacteria cell wall inhibitor

56
Q

Ethambutol blocks:

A

Arabinogalactan synthesis (cell wall)

57
Q

Cycloserine is a _____ inhibitor

A

Mycobacteria cell wall inhibitor

58
Q

Cycloserine inhibits:

A

Other cell wall synthesis enzymes like D-alanine-D-alanine synthetase and alanine racemase

59
Q

Alanine racemase is used in:

A

Mycolic acid synthesis

60
Q

Isoniazid excretion and metabolism

A

Excretion - renal
Metabolism - hepatic (50-90%)

61
Q

____ has a bimodal half life depending on ____.
50% of black and white individuals have a ____ half life, whereas 90% asians/Inuits have a ____ half life.

A

Isoniazid; race; Longer (3 hour); Shorter (1 hour)

62
Q

Name the cell wall inhibitors that work against mycobacteria

A

Isoniazid, Ethionamide, Ethambutol, Cycloserine

63
Q

Aminoglycosides are _____ inhibitors

A

Protein synthesis

64
Q

Protein synthesis inhibitors (7)

A
  • aminoglycosides
  • tetracyclines
  • macrolides
  • chlorampenicol
  • clindamycin
  • streptagramins
  • fusidic acid
65
Q

Streptomycin is a(n) _____

A

Aminoglycoside

66
Q

Aminoglycosides bind irreversibly to ____

A

30S ribosome

67
Q

Aminoglycosides are effective against ____ bacteria, but ____ are generally resistant

A

Aerobes; anaerobes

68
Q

Aminoglycosides are toxic to:

A

Ear and kidney
Ototoxicity.Chochleotoxicity

69
Q

Tetracyclines are _____ inhibitors

A

Protein synthesis (30S)

70
Q

Tetracyclines spectrum

A

Broad spectrum

71
Q

Tetracyclines should be avoided in which people?

A

Children under 8 years old
Pregnant/lactating women

72
Q

Those who have received tetracycline treatment may develop:

A

Unsightly tooth staining

73
Q

Linezolid is used to treat:

A

Penicillin and vancomycin resistant staphylococci, streptococci, enterococci

74
Q

Erythromycin, azythromycin, and clarithromycin are:

A

Macrolides

75
Q

Macrolides are _____ inhibitors

A

Protein synthesis (50S)

76
Q

Linezolid is a _____ inhibitor

A

Protein synthesis inhibitor

77
Q

First choice for penicillin allergic patients?

A

Macrolides (erythromycin)

78
Q

Chloramphenicol binds:

A

50S ribosome

79
Q

Chloramphenicol cannot be given in high doses or for a long time because:

A

They cause bone marrow aplasia (toxic)

80
Q

Clindamycin binds

A

50S ribosome

81
Q

Which antibiotic can treat VRSA and VRE (vancomycin resistant S. aureus/enterococcus)?

A

Streptagramins

82
Q

Streptagramins bind

A

50S

83
Q

Fusidic acid blocks what ribosome

A

50S ribosome

84
Q

Erythromycin has contraindications with:

A

Liver disease (hepatitis)

85
Q

Erythromycin metabolism and excretion

A

Hepatic (>95%), bile

86
Q

Nucleic acid inhibitors (3)

A
  • metronidazole
  • quinolones
  • rifampin
87
Q

Is metronidazole bacteriostatic or bactericidal?

A

Bactericidal

88
Q

Metronidazole blocks _____ in all _____

A

DNA synthesis; strict anaerobes

89
Q

Rifampin blocks:

A

RNA polymerase (inhibits RNA synthesis)

90
Q

If you need to treat mycobacteria resistant to Isoniazid, you can prescribe:

A

Rifampin

91
Q

Rifampin is bactericidal/bacteriostatic? It is very active against _____

A

Bactericidal; aerobic, gram-positive cocci

92
Q

Rifampin increases p450 CYP enzymes, which increase clearance for ____ (contraindication)

A

anti-HIV medications

93
Q

Someone with HIV and has Mycobacteria, they would likely be taking Isoniazid and anti-HIV drugs so they cannot be given ____

A

Rifampin

94
Q

Quinolones/fluoroquinolones inhibit

A

DNA gyrases/topoisomerases –> inhibit DNA replication

95
Q

Anti-metabolites (2)

A
  • sulfonamides
  • trimethoprim
96
Q

Sulfonamides inhibit ______. Poses potential complications with ____

A

Folic acid synthesis; pregnancy

97
Q

Folic acid is needed to make

A

Purines and pyrimidines (Dna synthesis)

98
Q

Trimethoprim inhibits ______ and is contraindicated in ____

A

dihydrofolate reductase; pregnancy

99
Q

Why is antibiotic resistance a problem in dentistry?

A

Oral bacteria (streptococci) may develop cross resistance to both penicillins and cephalosporins

100
Q

_____ rapidly acquires resistance while ____ rarely do so

A

S. aureus; S. pyogenes

101
Q

Resistance to some antibiotics like ____ is virtually unknown, whereas strains resistant to other drugs like ____ readily emerge

A

Metronidazole; penicillin

102
Q

Methicillin is relatively resistant to:

A

beta-lactamases

103
Q

Almost all S. aureus is sensitive to ____. However, ___ is emerging so vancomycin must be used instead. However, reports of ____ are not detected so linezolid or streptogramins must be used instead

A

Methicillin; MRSA; VRSA

104
Q

Types of resistance

A
  • primary (intrinsic) resistance
  • acquired resistance
  • cross-resistance
105
Q

Order of operation for antibiotic prescribing

A
  1. Penicillin
  2. Methicillin
  3. Vancomycin
  4. Linezolid
  5. Streptagramins
106
Q

Primary (intrinsic) resistance

A
  • naturally resistant to the drug
  • vancomycin ineffective in D-alanine-D-serine bacteria
107
Q

Acquired resistance

A
  • mutation or gene transfer
  • Rifampin ineffective against RNA polymerase mutation
  • beta lactamase transfer (R-plasmid)
108
Q

Cross-resistance

A
  • resistance to one drug confers resistance to related drugs (R-plasmids)
  • penicillin and cephalosporin resistance
109
Q

Mechanisms of resistance

A
  1. altered target - lower affinity for antibacterial but still functional
  2. altered uptake - increasing impermeability or increased efflux of drug out of cell
  3. drug inactivation - enzymes which modify or destroy the antibacterial agent
110
Q

Only documented plasmid to transfer in free-living environments

A

NDM-I (superbug)

111
Q

KPC

A

Klebsiella pneumoniae carbapenemase (superbug, ESBL)

112
Q

Four main treatments to reduce rejection of transplant

A
  1. methotrexate
  2. cyclosporin
  3. tacrolimus
  4. glucocorticoids (prednisone)
113
Q

Methotrexate (MTX) is often used in

A

chemotherapy and autoimmune disorders

114
Q

Methotrexate competitively inhibits

A

Dihydrofolate reductase (DHFR)

115
Q

Methotrexate inhibits ____ binding

A

IL-1 beta

116
Q

IL-1

A

inflammation

117
Q

Pharmacologic immunosuppression can present ____ and treat _____

A

graft vs host disease (GVHD); autoimmune disease

118
Q

Methotrexate is a treatment for

A

GVHD, autoimmune disorders (decreases inflammation)

119
Q

What drugs interact with methotrexate?

A
  1. penicillin (decreases elimination of MTX which can kill them)
  2. aminoglycosides (reduce absorption of MTX)
  3. NSAIDs have potentially fatal interactions
  4. nitrous oxide induces hematologic toxicity of MTX
120
Q

Cyclosporins are mainly used to treat ____ and prevent ____

A

Autoimmune diseases; GVHD

121
Q

Cyclosporin inhibits?

A

IL-2 and T-lymphocyte activity

122
Q

Tacrolimus interacts with

A

Macrolides

123
Q

Tacrolimus inhibits ____ production

A

IL-2

124
Q

Which is a more potent immunosuppressant - tacrolimus or cyclosporin?

A

Tacrolimus

125
Q

Tacrolimus is used to treat/prevent:

A

autoimmune disease; GVHD

126
Q

What drugs have contraindications with tacrolimus?

A
  1. macrolides (erythromycin)
  2. azoles )fluconazole)
127
Q

Tacrolimus is nto used with what patients?

A

Hep B/C patients

128
Q

Tacrolimus competed for:

A

CYP3A - cytochrome P450 liver enzymes

129
Q

Tacrolimus is influenced by _____. _____ make non-functional CYP3A5 protein, increasing risk of drug toxicity

A

Genetics; CYP3A5 G/G

130
Q

Glucorticoids (prednisone) treats _____; what effects does it have

A

Overactive immune diseases (high doses = immunosuppression)
- may result in T-cell or humoral immune deficiency, neutropenia

131
Q

Glucocorticoids inhibit what cytokines?

A

IL-1, IL-2, IL-4, IL-6, IL-8